NM_005359.6(SMAD4):c.845A>C (p.His282Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000580067.9

Allele description [Variation Report for NM_005359.6(SMAD4):c.845A>C (p.His282Pro)]

NM_005359.6(SMAD4):c.845A>C (p.His282Pro)

Gene:

SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.845A>C (p.His282Pro)

HGVS:

NC_000018.10:g.51058397A>C
NG_013013.2:g.95358A>C
NM_005359.6:c.845A>CMANE SELECT
NP_005350.1:p.His282Pro
NP_005350.1:p.His282Pro
LRG_318t1:c.845A>C
LRG_318:g.95358A>C
LRG_318p1:p.His282Pro
NC_000018.9:g.48584767A>C
NM_005359.5:c.845A>C

Protein change:

H282P

Links:

dbSNP: rs1555685962

NCBI 1000 Genomes Browser:

rs1555685962

Molecular consequence:

NM_005359.6:c.845A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000686559	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28135145, 34130653, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000686559

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 25, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

Co-occurrence of thyroid and breast cancer is associated with an increased oncogenic SNP burden.

Bakos B, Kiss A, Árvai K, Szili B, Deák-Kocsis B, Tobiás B, Putz Z, Ármós R, Balla B, Kósa J, Dank M, Valkusz Z, Takács I, Tabák Á, Lakatos P.

BMC Cancer. 2021 Jun 15;21(1):706. doi: 10.1186/s12885-021-08377-4.

PubMed [citation]

PMID:: 34130653
PMCID:: PMC8207626

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000686559.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces histidine with proline at codon 282 of the SMAD4 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individuals affected with colorectal cancer and breast cancer (PMID: 28135145, 34130653). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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